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Total Synthesis and Bioactivity Mapping of Geodiamolide H.

ABSTRACT: The first total synthesis of the actin-stabilizing marine natural product geodiamolide H was achieved. Solid-phase based peptide assembly paired with scalable stereoselective syntheses of polyketide building blocks and an optimized esterification set the stage for investigating the key ring-closing metathesis. Geodiamolide H and synthetic analogues were characterized for their toxicity and for antiproliferative effects in cellulo, by characterising actin polymerization induction in vitro, and by docking on the F-actin target and property computation in silico, for a better understanding of structure-activity relationships (SAR). A non-natural analogue of geodiamolide H was discovered to be most potent in the series, suggesting significant potential for tool compound design.

SUBMITTER: Nasufovic V

PROVIDER: S-EPMC8453818 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Total Synthesis and Bioactivity Mapping of Geodiamolide H.

Nasufović Veselin V Küllmer Florian F Bößneck Johanna J Dahse Hans-Martin HM Görls Helmar H Bellstedt Peter P Stallforth Pierre P Arndt Hans-Dieter HD

Chemistry (Weinheim an der Bergstrasse, Germany) 20210625 45

The first total synthesis of the actin-stabilizing marine natural product geodiamolide H was achieved. Solid-phase based peptide assembly paired with scalable stereoselective syntheses of polyketide building blocks and an optimized esterification set the stage for investigating the key ring-closing metathesis. Geodiamolide H and synthetic analogues were characterized for their toxicity and for antiproliferative effects in cellulo, by characterising actin polymerization induction in vitro, and by ...[more]

PMID: 34032329

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